The long term objective of this proposal is to induce a protective mucosal immune response to prevent HIV-1 infection. The transmission of SIV and HIV through the vaginal mucosa to macaques, chimpanzees and humans has been reported. We propose to immunize orally with recombinant defective SIV-like particles lacking the genomic RNA (gag-env), entrapped in microcapsules of lactige-glycolide copolymer in order to stimulate a mucosal immune response in mice. To protect the antigens against degradation during the passage through the stomach juices, the gag-env will be incorporated into different preparations of lactide glycolide microcapsules. The effectiveness of the microcapsule in protecting the immunogenicity of the gag-env will be established by treating the microcapsules with stimulated gastric and intestinal juices and the resulting protein will be characterized by immunoblot and SDS-PAGE analysis. The optimized microcapsules will be administered to mice orally in parallel with gag-env in solution. The antibody response in serum, saliva and lavages from the gut and the vagina of immunized mice will be determined. In the phase II part of the proposal we propose to study the response of immunized macaques challenged with SIV through the vaginal route.